PROJECT SUMMARY/ABSTRACT Justin Echouffo Tcheugui, MD, PhD is an Assistant Professor in the Division of Endocrinology at the Johns Hopkins University School of Medicine. He seeks a K23 Mentored Patient-Oriented Research Career Development Award to obtain essential skills and mentored research experience for an independent career as a physician scientist in the field of metabolism and cardiovascular diseases. His research proposal details a five-year plan, with an overarching goal of achieving a clinical, biomarker and imaging characterization of diabetes-related cardiac dysfunction including an identification of key pathways of pathogenicity, in a large community-based cohort of black and white adults, and in a clinic-based sample of individuals with diabetes. The specific aims of the research are: 1) Assess the association of hyperglycemia with longitudinal changes in cardiac structure and function, and incidence and progression of heart failure and its subtypes; 2) Identify novel molecular pathways underlying the occurrence of diabetes-related cardiac dysfunction, using a plasma proteomic approach; 3) Evaluate whether coronary microvascular disease is a specific marker of diabetes- related cardiac dysfunction, using a dual investigative approach including cardiac positron emission tomography (PET) and circulation biomarkers of microvascular dysfunction. This study will inform heart failure prevention and treatment among individuals with diabetes, as it may identify novel biomarkers associated with diabetes-related cardiac dysfunction that can enhance our understanding of pathophysiology and serve as potential targets for interventions in future studies. Concurrent to the proposed research, the applicant will have tailored, in-depth didactic and hands-on training in advanced epidemiologic and biostatistics methods, biomarker and proteomics research, and in cardiac PET as an investigative imaging technique, as well as develop expertise in the design and performance of clinical studies, by leading data collection in a new cohort. The acquired skills will fill key training gaps for the applicant, thereby positioning Dr. Echouffo Tcheugui for a successful independently funded research career. His long-term goals are to establish a research program aimed at advancing the understanding of cardiovascular complications in diabetes, and informing future strategies for cardiovascular risk prediction and prevention among individuals with diabetes.